Depressed individuals have been found consistently to report a higher incidence of recent severe stress than nondepressed people. Further, compared with patients without a recent severe life event, depressed patients with severe stress may have more severe symptoms, a different clinical course, and different rates of remission. Collectively, these findings suggest that the presence of recent severe stress represents a marker of potentially important individual differences in depression. Because not all people who encounter severe stress develop depression, however, information on other risk factors is required to understand individual differences in vulnerability to depression in the face of life stress. The construct of cognitive biases has been prominent in major theories of depression, and has been postulated to be important in relation to life stress and depression. Despite the obvious relevance of research that integrates information across social (life stress) and psychological (cognitive) domains, such inquiry has proven difficult to undertake. The methodological intricacies within each domain present a number of practical and logistic obstacles. Moreover, there are conceptual difficulties that have hindered this integration. Longitudinal empirical work, guided by theoretical insights and based on state-of-the-art methods from each domain, is required to advance understanding of multifactorial, integrative research. The primary goal of the present project is to investigate life stress and cognitive information processing biases for depression within the conceptual scheme afforded by diathesis-stress theory. The present research has three specific aims. First, we test the relationship between life stress and cognitive bias within a well-differentiated conceptual scheme afforded by diathesis-stress theory and informed by attention to the issue of etiologic heterogeneity of depression; state-of-the-art methods will be used to assess life stress and cognitive vulnerability. Second, we test the predictive utility of stress, cognitive bias, and their interaction for clinical features and treatment course of depression. Third, we test differential activation of cognitive biases in remitted depressives as a function of preonset life stress with a laboratory mood priming paradigm to address questions of cognitive vulnerability. Secondary aims include testing: (1) other forms of life stress in relation to cognitive vulnerability; (2) life stress measurement issues; and (3) associations between stress-cognition interactions and other clinically relevant (e.g., attrition, treatment-seeking, post-recovery course) phenomena.